Conventional ideas concerning the pathogenesis of psoriasis have now expanded to include the compelling hypothesis that activated T cells influence the proliferation of keratinocytes. Because T cells must first be recruited from extracutaneous sources, T cell participation in inducing or maintaining the psoriatic phenotype critically depends upon mechanisms of T-cell extravasation in skin. In fact, it is now known that lymphocytes are a uniquely mobile population of cells that exhibit non- random trafficking mechanisms; previous work has demonstrated that, in humans, skin-selective T cell homing is mediated by the reciprocal interaction of the cutaneous lymphocyte-associated antigen (CLA) on T cells and E-selectin (formerly known as ELAM-l) on inflamed dermal endothelium. Previous work has also shown that T cells in psoriasis, like other inflammatory dermatoses, are CLA+, and superficial dermal venules in psoriasis are E-selectin+, consistent with a critical role for the CLA/E- selectin adhesion system in T cell homing to psoriatic lesions. This Pilot and feasibility Project will address the regulation of this receptor-ligand pair in patients with psoriasis. Our working hypothesis is that utilization or regulation of this CLA/E-selectin system is abnormal in patients with psoriasis, allowing excessive recruitment of "psoriatic effector cells". Specific aims are: l) to determine the expression kinetics of CLA by multiparameter flow cytometry on T cells obtained from suction blisters placed over: lesional skin in patients with psoriasis, delayed type-hypersensitivity (DTH) reactions in non-lesional psoriatic skin, and DTH reactions in normal subjects, 2) to assess the capacity of blister fluid supernatants to induce CLA expression on PHA and IL-2 stimulated T cells, 3) to compare the kinetics of E-selectin expression on venular endothelium (by immunohistology) within biopsies of DTH reactions placed on selected psoriasis patients and normal control subjects, 4) to assess the effect of two effective therapeutic interventions (UVB radiation or methotrexate) on T cell activities observed in aims 1-3, and 5) to search for potential recirculating "psoriatic effector T cells" (i.e., CLA(high) T cells) by multiparameter flow cytometry. Evidence that unique aspects of CLA/E-selectin utilization do occur in patients with psoriasis will lead to an application to investigate the regulation of this system.